Abstract Details

Title Functional Characterization of Reappearing B cells After Anti-CD20 Mediated B cell Depletion in Two Animal Models of Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) S26 - MS and CNS Inflammatory Disease: Clinical Considerations II (1:33 PM-1:44 PM)

Poster/Presentation
Number 004

Background Recent trials revealed that repetitively applied anti-CD20 antibodies reduce the frequency of relapses and development of central nervous system (CNS) lesions in multiple sclerosis (MS). However, it is largely unknown whether patients with MS or related demyelinating disorders must be continuously depleted of B cells to achieve this benefit or whether alternatively anti-CD20 intervention can lastingly reset disease-driving B cell function.

Objective Characterization of reappearing CD20⁺ B cells in the bone marrow, blood and secondary lymphoid organs after transient anti-CD20 treatment in murine experimental autoimmune encephalomyelitis (EAE).

Design/Methods C57BL/6 mice received 3 weekly subcutaneous injections of 0.2 mg murine anti-CD20 or control antibody prior to immunization with a) MOG peptide p35-55, a setting in which B cells remain naive or b) MOG protein 1-117, a setting in which B cells get activated. Reappearing B cells were phenotypically analyzed for expression of activation markers, co-stimulatory molecules, B cell receptor diversity and antigen presentation function.

Results In both models, a fraction of CD20⁺ antigen-experienced B cells persisted in splenic follicles despite extensive systemic anti-CD20 application. Upon treatment cessation, CD20⁺ B cells simultaneously repopulated in bone marrow and spleen before their reappearance in blood. Returning B cell population, showed a shift towards mature, differentiated phenotypes containing an increased frequency of myelin-reactive B cells with restricted B cell receptor gene diversity and enhanced capability to activate myelin-specific T cells in the model in which B cells are intrinsically activated. By contrast, in the T cell-mediated EAE model, B cells reappeared in a predominantly naïve status with a relative loss of pathogenic APC function.

Conclusions These findings highlight that distinct subpopulations of B cells differ in their sensitivity to anti-CD20 treatment and suggest that differentiated B cells persisting in secondary lymphoid organs contribute to the recovering B cell pool.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
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	No disclosure on file
Scott S. Zamvil, MD, PhD, FAAN (University of CA, San Francisco)	Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genzyme. Dr. Zamvil has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Horizon. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. The institution of Dr. Zamvil has received research support from Sumaira Foundation. Dr. Zamvil has received personal compensation in the range of $5,000-$9,999 for serving as a Advisory Board with Genzyme. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board with Genentech. Dr. Zamvil has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board with Alexion.
Wolfgang Brueck, PhD (Zentrum Pathologie)	Dr. Brueck has nothing to disclose.
Klaus Lehmann-Horn, MD	No disclosure on file
	No disclosure on file

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